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The protein encoded by this gene belongs to the Ser/Thr protein kinase family. It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2011]
CHEK1 (Checkpoint Kinase 1) is a Protein Coding gene. Diseases associated with CHEK1 include Ovarian Cancer and Ataxia-Telangiectasia. Among its related pathways are ATM Pathway and Homologous DNA Pairing and Strand Exchange. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity.
Checkpoint kinases (Chks) are serine/threonine kinases that are involved in the control of the cell cycle. Two subtypes have so far been identified, Chk1 and Chk2. They are essential components to delay cell cycle progression in all cells and act at all three cell cycle checkpoints.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA,IMP | 22024163 |
GO:0004674 | protein serine/threonine kinase activity | TAS | -- |
GO:0005515 | protein binding | IPI | 11836499 |
GO:0005524 | ATP binding | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000781 | colocalizes_with chromosome, telomeric region | IDA | 15149599 |
GO:0000785 | chromatin | ISS | -- |
GO:0000794 | condensed nuclear chromosome | IDA | 9382850 |
GO:0005615 | extracellular space | HDA | 23580065 |
GO:0005634 | nucleus | IBA,IDA | 15311285 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | DNA Double-Strand Break Repair |
.53
DNA damage_DNA-damage-induced responses
.01
|
|
2 | Regulation of activated PAK-2p34 by proteasome mediated degradation | ||
3 | Homologous DNA Pairing and Strand Exchange |
.01
|
|
4 | DNA Damage Response | ||
5 | Chks in Checkpoint Regulation |
Chks in Checkpoint Regulation
.58
G2-M Phase Transition
.58
|
DNA Repair Mechanisms
.31
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000077 | DNA damage checkpoint | IMP | 19716789 |
GO:0000086 | G2/M transition of mitotic cell cycle | IEA | -- |
GO:0001833 | inner cell mass cell proliferation | IEA | -- |
GO:0006260 | DNA replication | TAS | -- |
GO:0006281 | DNA repair | IMP | 19716789 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Lacosamide | Approved | Pharma | inhibitor | Checkpoint kinase inhibitor,ATP competitive, Checkpoint kinase (Chk) inhibitor | 90 | |
fostamatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors | 0 | |
Floxuridine | Approved | Pharma | Antineoplastic antimetabolite, Inhibitor of thymidylate synthetase; anticancer agent, RNA and DNA synthesis inhibitor | 56 | ||
CHIR-124 | Experimental | Pharma | Target | Chk1 inhibitor,novel and potent | 0 | |
(2R)-1-[(5,6-DIPHENYL-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)AMINO]PROPAN-2-OL | Experimental | Pharma | Target | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
||
DIM |
|
1968-05-4 |
|
|
||
PD 407824 |
|
622864-54-4 |
|
|
Compound | Action | Cas Number |
---|---|---|
DIM | Activates Chk2; induces G2/M cell cycle arrest | 1968-05-4 |
NSC 109555 ditosylate | Selective Chk2 inhibitor | 66748-43-4 |
PD 407824 | Selective inhibitor of Chk1 and Wee1 | 622864-54-4 |
SB 218078 | Inhibitor of checkpoint kinase 1 (Chk1) | 135897-06-2 |
TCS 2312 | Potent Chk1 inhibitor | 838823-31-7 |
Compound | Action | Cas Number |
---|---|---|
AZD7762 | Checkpoint kinase inhibitor,ATP competitive | 860352-01-8 |
CCT244747 | Potent and selective CHK1 inhibitor | 1404095-34-6 |
CHIR-124 | Chk1 inhibitor,novel and potent | 405168-58-3 |
Chk1 and MK2 Inhibitors set | Chk1- and MK2 inhibitors | |
Floxuridine | Antineoplastic antimetabolite | 50-91-9 |
LY2603618 | Chk1 inhibitor,highly selective | 911222-45-2 |
LY2606368 | CHK1 inhibitor | 1234015-52-1 |
MK-8776 (SCH-900776) | Chk1 inhibitor,potent and selective | 891494-63-6 |
NSC 109555 ditosylate | 66748-43-4 | |
PF-477736 | Chk1 inhibitor | 952021-60-2 |
SCH900776 S-isomer | Checkpoint kinase(Chk)inhibitor | 891494-64-7 |
TCS 2312 | 838823-31-7 |
ExUns: | 1a | · | 1b | · | 1c | · | 1d | ^ | 2a | · | 2b | · | 2c | ^ | 3 | ^ | 4 | ^ | 5a | · | 5b | ^ | 6 | ^ | 7a | · | 7b | ^ | 8 | ^ | 9a | · | 9b | · | 9c | · | 9d | ^ | 10a | · | 10b | ^ | 11 | ^ | 12 | ^ | 13a | · | 13b | ^ | 14 | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||
SP4: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||
SP6: | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP7: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP8: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP9: | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP10: | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP11: |
ExUns: | 15 | ^ | 16 |
---|---|---|---|
SP1: | |||
SP2: | |||
SP3: | |||
SP4: | |||
SP5: | |||
SP6: | |||
SP7: | |||
SP8: | |||
SP9: | |||
SP10: | |||
SP11: |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | CHEK1 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | CHEK1 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | CHEK1 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | CHEK1 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | CHEK1 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Chek1 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Chek1 30 |
|
||
Chicken (Gallus gallus) |
Aves | STT3A 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | CHEK1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | chek1 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | LOC398191 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | chek1 30 31 |
|
OneToOne | |
efnb1 30 |
|
||||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.1073 30 |
|
||
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP008118 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | grp 30 31 32 |
|
OneToOne | |
Worm (Caenorhabditis elegans) |
Secernentea | chk-1 30 31 |
|
OneToMany | |
DC2.7b 32 |
|
|
|||
R02C2.2 32 |
|
|
|||
DC2.7a 32 |
|
|
|||
Y43D4A.6 31 32 |
|
OneToMany | |||
R02C2.1 31 32 |
|
OneToMany | |||
kin-34 31 |
|
OneToMany | |||
R02C2.6 31 |
|
OneToMany | |||
kin-33 31 |
|
OneToMany | |||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | CHK1 30 31 33 |
|
OneToOne | |
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0F01276g 30 |
|
||
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_AEL185C 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToOne | |
Bread mold (Neurospora crassa) |
Ascomycetes | NCU08346 30 |
|
||
Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | chk1 30 |
|
||
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.1196 30 |
|
SNP ID | Clinical significance and condition | Chr 11 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
745869 | Benign: not provided | 125,644,503(+) | G/A | INTRON_VARIANT | |
rs114579795 | Likely Benign: Hereditary cancer-predisposing syndrome | 125,629,059(+) | C/T | INTRON_VARIANT | |
rs1314180672 | Likely Pathogenic: Ovarian Neoplasms | 125,627,605(+) | A/T | SPLICE_ACCEPTOR_VARIANT,INTRON_VARIANT | |
rs139144317 | Likely Benign: Hereditary cancer-predisposing syndrome | 125,654,744(+) | T/C | INTRON_VARIANT | |
rs141004252 | Likely Benign: Hereditary cancer-predisposing syndrome | 125,627,913(+) | T/G | INTRON_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
ovarian cancer |
|
|
ataxia-telangiectasia |
|
|
fanconi anemia, complementation group a |
|
|
li-fraumeni syndrome |
|
|
breast cancer |
|